Features of DNA Repair in Dermal Fibroblasts in Ataxia-Telangiectasia Patients with Mosaic Type of Manifestation of Active ATM Kinase

Cell mosaicism is found in biological systems much more often than clinically identified forms of the disease, in some cases, "erased forms” or "normal variants” are phenotypic manifestations of mosaicism. Some diseases, difficult for a clinical diagnosis, such as ataxia-telangiectasia, are based on cell mosaicism. This work is aimed to study DNA repair disorders in the cell lines of dermal fibroblasts isolated from skin biopsies of 5 patients with a clinically diagnosed ataxia-telangiectasia. In the obtained cell lines, the method of indirect immunofluorescence was used to determine the number, intensity, focus area pATMSer1981 and 53BP1, as well as the number of cells with the active form of the ATM kinase. The mosaic pattern of malfunctioning of the active form of the ATM kinase, phospho-ATM Ser1981, was revealed at different time intervals after exposure to ionizing radiation at a dose of 2 Gy. Significant differences were found between the number of ATMSer1981 and 53BP1 foci, the fluorescence intensity and their area in the cells of patients with ataxia-telangiectasia and healthy donors. The results of this work can be used in the diagnosis of ataxia-telangiec-tasia and determining the degree of impairment of the functional activity of the ATM gene.